Impact of antibiotics, corticosteroids, and microbiota on immunotherapy efficacy in patients with non-small cell lung cancer
María Zapata-García, Alba Moratiel Pellitero, Dolores Isla, Eva Heredero Gálvez, Marta Gascón Ruiz, Andrea Sesma, Raquel Barbero, Javier Galeano, Rosa del Campo, Maitane Ocáriz, Elisa Quílez, Mara Cruellas, Ariel Remírez-Labrada, Julián Pardo, Luis Martínez‐Lostao, María Pilar Domingo, Patricia Esteban, Irene Torres-Ramón, Alfonso Yubero, José Ramón Paño, Rodrigo Pimienta Lastra
Abstract
Lung cancer is a leading cause of morbidity and mortality globally, with its high mortality rate attributed mainly to non-small cell lung cancer (NSCLC). Although immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized its treatment, patient response is highly variable and lacking predictive markers. We conducted a prospective study on 55 patients with NSCLC undergoing ICI therapy to identify predictive markers of both response and immune-related adverse events (IrAEs) in the airway microbiota. We also analyzed the clinical evolution and overall survival (OS) with respect to treatments that affect the integrity of the microbiota, such as antibiotics and corticosteroids. Our results demonstrated that respiratory microbiota differ significantly in ICI responders: they have higher alpha diversity values and lower abundance of the Firmicutes phylum and the Streptococcus genus. Employing a logistic regression model, the abundance of Gemella was the major predictor of non-ICI response, whereas Lachnoanaerobaculum was the best predictor of a positive response to ICI. The most relevant results were that antibiotic consumption is linked to a lower ICI response, and the use of corticosteroids correlated with poorer overall survival. Whereas previous studies have focused on gut microbiota, our findings highlight the importance of the respiratory microbiota in predicting the treatment response. Future research should explore microbiota modulation strategies to enhance immunotherapy outcomes. Understanding the impact of antibiotics, corticosteroids, and microbiota on NSCLC immunotherapy will help personalize treatment and improve patient outcomes.